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Pulmonary fibrosis is one of the conditions that occur in Post-COVID Syndrome patients. Development of specific treatment as an agent to treat pulmonary fibrosis is still ongoing. Ferulic acid is a compound that has a potential lung antifibrotic agent through inhibition of TGF-β1-mediated signaling. Molecular docking studies using the AutoDock Tools program version 1.5.7 were conducted on ferulic acid and its analogs to determine the activity of compounds as antifibrotic. Furthermore, the interaction of the compound with the receptor was visualized using the Discovery Studio 2021 program. The results showed that ferulic acid and its analogs have lower free energy than pirphenidone which is a standard lung antifibrotic drug. 4-benzoyloxy-3-methoxycinnamic acid is the compound that has the greatest activity. The group that contributes to the ligand-receptor interaction is the aromatic group with n interaction. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic medications, one of cancer chemo preventive mechanism were permitted for different cancers. Nevertheless, major primary and secondary resistance obstruct efficacy in several tumor types. Moreover, the improvement of safe and effective NSAIDs for angiogenesis inhibition is complicated, because of their serious toxicity. So, we require improving clinically appropriate strategies to boost efficacy of anti-angiogenic drugs with low risk of toxicity. Objectives: The present study aimed to synthesize the (E)-3- (3-methoxyphenyl)propenoic acid (3MPCA), to determine the anti-angiogenic activity and predict its toxicity. Methods: 3MPCA was obtained by Knoevenagel reaction using microwave irradiation at 400 Watt. The anti-angiogenesis experimental was performed using chorioallantois membrane of embryonated chicken eggs induced by b-FGF. The potency of 3MPCA was verified at dosage 30 and 60 ng and compared with celecoxib 60 ng. Toxicity prediction of 3MPCA was performed by ProTox II online program. Results: The results showed that 3MPCA was achieved in good yield (89%). Anti angogenic activity was showed by endothelial cells growth in neovascular capillaries of new blood vessel of chorioallantois membrane of embryonated chicken eggs. The endothelial cells growth decreased until 41.7-83%. The prediction LD50 was 1772mg/kg. Conclusion: (E)-3-(3-methoxyphenyl)propenoic acid can be obtained through Knovenagel reaction using microwave irradiation and it has potential as anti-angiogenesis inhibitor with low toxicity. [ABSTRACT FROM AUTHOR]

Background: Indonesia is the world's primary producer of clove. In order to find new utilization for clove and new biologically active compounds, eugenol, the main constituent of clove, has been converted to its derivatives. Objective: This study aims to examine in vivo anticancer activity of benzoxazine and aminomethyl compounds derived from eugenol. Methods: Fibrosarcoma was induced by injection of benzo(a)pyrene solution. The test compounds were given per oral at 20, 40, and 80 mg/Kg body weight, once a day for 30 days. Results: As a result, all the tested compounds showed activity in reducing the cancer incidence rate. All the tested compounds were also found to reduce tumor weight. Benzoxazine derivatives gave slightly better activity compared to aminomethyl derivatives. The strongest activity was exhibited by 6-allyl-3-(furan-2-ylmethyl)-8-methoxy-3,4-dihydro-2H-benzo(e)(1,3)oxazine. Conclusions: All four benzoxazine and aminomethyl compounds derived from eugenol that were tested exhibited anticancer activity in mice fibrosarcoma. [ABSTRACT FROM AUTHOR]

Background: Coronary Heart Disease (CHD), commonly known as the silent killer, impacted the severity of COVID-19 patients during the pandemic era. Thrombosis or blood clots create the buildup of plaque on the coronary artery walls of the heart, which leads to coronary heart disease. Cyclooxygenase 1 (COX-1) is involved in the production of prostacyclin by systemic arteries; hence, inhibiting the COX-1 enzyme can prevent platelet reactivity mediated by prostacyclin. To obtain good health and well-being, the research of discovery of new drugs for anti-thrombotic still continue. Objective: This study aims to predict the potential of 17 compounds owned by the vanillin analog to COX-1 receptor using in silico. Methods: This research employed a molecular docking analysis using Toshiba hardware and AutoDock Tools version 1.5.7, ChemDraw Professional 16.0, Discovery Studio, UCSF Chimera software, SWISSADME and pKCSM, a native ligand from COX-1 (PDB ID: 1CQE) was validated. Results: The validation result indicated that the RMSD was <2 Å. The 4-formyl-2-methoxyphenyl benzoate compound had the lowest binding energy in COX-1 inhibition with a value of -7.70 Å. All vanillin derivatives show good intestinal absorption, and the predicted toxicity indicated that they were non-hepatotoxic. All these compounds have the potential to be effective antithrombotic treatments when consumed orally. Conclusion: In comparison to other vanillin derivative compounds, 4-formyl-2-methoxyphenyl benzoate has the lowest binding energy value; hence, this analog can continue to be synthesized and its potential as an antithrombotic agent might be confirmed by in vivo studies. [ABSTRACT FROM AUTHOR]

Background: p-methoxycinnamic acid (pMCA) is an ethyl pmethoxycinnamic derivative, which is the largest active ingredient in the rhizome of the kencur (Kaempferia galanga L) plant. Several studies reported that the compound has anti-inflammatory activity but has low solubility in water. The formation of a pMCA-ß-cyclodextrin (ßCD) inclusion complex with a molar ratio of 1:1 can increase its solubility. The formation of inclusion complexes with conventional methods requires a long time and the yield value is not optimal. Objective: This study aims to evaluate the dissolution of the pMCA-ßCD inclusion complex produced using the microwave irradiation method. Methods: The product was manufactured with chloroform solvent and a power of 400 watts (power 80%). It was then evaluated using the Differential Thermal Analysis (DTA) every 2 minutes until the 8th minute. The reaction was complete after 4 minutes of treatment with a yield of 96.5%. The obtained inclusion complexes were evaluated using DTA, FTIR, and PXRD. Subsequently, a dissolution test was carried out using a type 2 apparatus in distilled water medium of pH 6.8±0.05 at 37±0.5°C. Results: The results showed that there was a change in the melting temperature profile, infrared spectra, and crystallinity of the product. An 89.18% dissolution was also obtained within 60 minutes, which was twice that of pMCA compounds. Conclusion: From the results of the study, it can be concluded that the formation of pMCA-ßCD inclusion complexes using the microwave irradiation method is capable of providing high-yield values in a short time. [ABSTRACT FROM AUTHOR]

Currently, Canine coronavirus (CCoV) is an enteric pathogen of the Alphacoronavirus-1 species that causes mild to severe diarrhea in puppies. The pathogenesis of this infection will cause severe lymphopenia and lead to death in puppies. This study aimed to determine the administration of probiotics on TNF-α expression, histological findings of the liver and lung in mice infected with CCoV. A total of 28 mice were randomly assigned into seven treatment groups, i.e. (C-) placebo; (C+) active CCoV vaccine induction; (T1) CCov + Isopronosin; (T2) CCoV + Lactobacillus acidophilus probiotic; (T3) CCoV + Lactobacillus Acidophylus and Bifidobacterium probiotics; (T4) CCoV + colustrum fermentation probiotic; (T5) CCoV + ginger, turmeric and ginger probiotics. Thereafter, the expression of TNF-α in the duodenum was stained using immunohistochemistry, liver and lung were stained using hematoxylin eosin. The data were analyzed using the ANOVA test followed by the Tukey test with a significance level (p<0.05). TNF-α expression on T4 and T5 decreased significantly (p<0.05) compared to C+, T1, T2 and T3. Histologic findings of the liver in the C- and T4 groups showed normal features in the central vein. On the other hand, glycogen accumulation was found in hepatocyte cells, hemorrhage with sinusoid dilation, lymphocyte infiltration in centro lobular area in group C+. Lung histology showed normal features of sinusoids and alveolar septa in groups C- and T4. Meanwhile, intra-alveolar hemorrhage was found with neutrophil cell infiltration and fibrin plasma accumulation in group C+. In conclusion, colostrum fermentation probiotics can reduce TNF-α expression in the duodenum and improve the liver and lung physiology in mice infected with CCoV. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to verify the antiangiogenic activity of ferulic acid (FA) and its potency to inhibit cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expression in the chorioallantoic membrane (CAM) model. Moreover, we verified its mechanism of action by docking the molecule on COX-2, tyrosine kinase, and VEGF-2 proteins in silico. Materials and Methods: An antiangiogenesis assay of FA at doses of 30, 60, and 90 µg was performed using the CAM of chicken eggs that were 9 days old and stimulated by 60 ng of basic fibroblast growth factor. Celecoxib (60 µg) was used as the reference drug. The inhibitory activity on VEGF and COX-2 expression was determined by immunohistochemistry assay. Molecular docking of FA was accomplished by Molegro Virtual Docker program ver. 5.5 on COX-2 enzyme (PDB ID 1CX2), tyrosine kinase receptor (PDB ID 1XKK), and VEGF-2 receptor (PDB ID 4ASD). Results: FA at doses of 30, 60, and 90 µg significantly prevented angiogenesis in the CAM model, which was represented as inhibitory activity against endothelial cells of blood vessels (42.6-70.7%) and neovascularization (43.0-86.6%). The inhibitory activity of FA against VEGF expression was stronger than its action on COX-2 expression. Molecular docking on VEGF-2 receptor resulted in an RS value of FA of -73.844 kcal/mol and for celecoxib it was -94.557 kcal/mol. The RS value on tyrosine kinase of FA was -84.954 kcal/mol, while on celecoxib it was -93.163 kcal/mol. Docking on COX-2 receptor gave an RS value of FA of -73.416 kcal/mol, while for celecoxib it was -118.107 kcal/mol. Conclusion: Reductions in VEGF-2 and COX-2 expression due to treatment with FA at the dose range 30-90 µg appeared to be related to angiogenesis inhibition, which was shown by two parameters, namely inhibition of neovascularization and endothelial cell growth in blood vessels. It was concluded that FA is a promising antiangiogenic therapeutic agent especially at the early stage, and this activity can arise from inhibitory action on COX-2 and VEGF-2 proteins. [ABSTRACT FROM AUTHOR]

P2Y12 is a platelet receptor that is involved in ADP signal transduction and is an attractive target for antithrombotic drugs. The side effects of antithrombotic drugs are not pleasant for the patient, so research into the development of new antithrombotic agents is still necessary. Evaluation of absorption, distribution, metabolism, elimination, and the toxicity profile of candidate drugs is an important step in drug development. The aim of this study was to predict the potency of ferulic acid (FA) and its derivatives (FA1-24) as antiplatelet drugs by a docking study on the P2Y12 receptor (PDB ID: 4PXZ) and their ADMET performance. The docking study was performed using Molegro Virtual Docker, version 5.5. ADMET prediction of FA was conducted using the pkCSM online tool. The results of the in silico study showed that FA-19 had the lowest MolDock score (MDS), which means that this compound is predicted to have the greatest activity. FA-19 is also predicted to be practically non-toxic. It is expected that FA-19 will have good intestinal absorption and is similarly distributed in the intestine and in the blood plasma. Its penetration in the bloodbrain barrier is moderate but does not inhibit the CYP2D6 and CYP3A4 enzymes. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the top causes of death worldwide. A wide range of illnesses known as cancer can start in almost any organ or tissue in the body when abnormal cells multiply uncontrollably. Cancer patients have higher levels of the Topo IIa protein in their cells, this protein has been proposed as a relevant target for anticancer treatment development. Objective: This study aims to predict the anticancer activity of pinostrobin and 5-Oacylpinostrobin derivatives against topoisomerase IIa by docking molecular and QSAR study. Methods: In silico analysis was performed using the structure of the topoisomerase IIa (PDB: 5GWK)) as templates. Molecular docking analysis was performed with AutoDock Vina. Result: All 5-O-acyl pinostrobin derivatives, showed lower ΔG values than the parent pinostrobin. The 5-O-acetyl pinostrobin compound showed the highest score, namely - 9.14 kcal/mol. 5-O-acetyl pinostrobin is predicted as the most powerful inhibitor that can cause inhibition of topoisomerase IIa. Conclution: The results of the best QSAR equation obtained can be used as a reference for predicting the activity of the new pinostrobin derivatives to be synthesized by inserting the electronic (Etot) parameter values of the compounds into the equation. [ABSTRACT FROM AUTHOR]

Background: Currently Mycobacterium tuberculosis is found to be resistant to the treatment of tuberculosis with rifampin and isoniazid (INH) and often stated as multi-drug resistance (MDR). Knowledge and determination of biological properties of plant extracts is a source of drug candidates in various health fields. Therefore, natural products are important in the discovery of new drugs, especially in disease therapy, particularly for tropical diseases, tuberculosis. Brucea javanica, known as Buah Makasar, is found in many Asian countries including Indonesia. This plant fruit has a very bitter taste so it cannot be directly consumed and is often used as a traditional medicine to prevent some diseases, especially malaria. There has been no research on the effectiveness of Buah Makasar in tuberculosis. Objective: This study aims to identify compounds contained in Brucea javanica, namely bruceines, bruceosides and yadanziosides in inhibiting the InhA enzyme found in the wall of Mycobacterium tuberculosis. Methods: This in-silico study is using Molegro Virtual Docker (MVD) Ver. 5.5. We compared it to the native ligand, namely N-(4-Methylbenzoyl)-4-Benzylpiperidine (code: 4PI) and the reference drug standard, INH. Results: In-silico results show that yadanziosides found in Brucea javanica have the potential to inhibit the InhA enzyme. Bruceoside F (-190.76 Kcal/mol) has the lowest MolDock score among the 27 other compounds. It is also having lower MolDock score than the native ligand 4PI (-120.61 Kcal/mol) and INH (- 54.44 Kcal/mol). Conclusion: Brucea javanica can be considered as source of drug development for againts tuberculosis. [ABSTRACT FROM AUTHOR]

Background: Cinnamic acid and its derivatives have been widely studied for their efficacy because of the pharmacological effect on good health and well being. Microwave irradiation is more time effective to synthesize than conventional heating method because it conducts heat faster and shortens the reaction time. Objective: This study aimed to synthesize 4-hydroxy-3-methoxycinnamic acid using microwave irradiation and its antiplatelet activity by blood clotting time method. Methods: Synthesis of 4-hydroxy-3-methoxycinamic acid with malonic acid and 4-hydroxy-3-methoxybenzalehyde as a starting material using ammonium acetate catalyst with microwave irradiation (960 Watt, 4 minutes). The synthesis results were tested for purity by thin-layer chromatography, a melting point determination and structure identification (UV-Vis, infrared, and proton NMR spectrometry). The antiplatelet activity test consisted of a negative control group CMC-Na, a positive control acetosal, cinnamic acid, and 4-hydroxy-3-methoxycinnamic acid, each group consisted of 3 different doses, namely 0.0037 mmol/Kg (I), 0.0069 mmol/Kg (II) and 0.0139 mmol/Kg (III). Results: Synthesis of 4-hydroxy-3-methoxycinamic acid had a yield percentage of 30.55%. The test results showed that the 4-hydroxy-3-methoxycinnamic acid compound has antiplatelet activity with an ED30 value of 1.3080 mg/Kg BW and antiplatelet activity comparable to acetosal. Conclusion: 4-hydroxy-3-methoxycinamic acid can be synthesized by microwave irradiation and had antiplatelet activity 1.7 fold greater than cinnamic acid. [ABSTRACT FROM AUTHOR]

Background: Urea derivatives showed good analgesic activity compared to diclofenac sodium. The addition of the allyl group to the thiourea and 4-tertiary-butylbenzoyl chlorideis expected to provide a better analgesic effect. Objective: The research aimed to synthesize 1-allyl-3-(4-tertiary-Butylbenzoyl) Thiourea and determine its analgesic activity in mice (Mus musculus). Methods: The synthesis was carried out by a modified Schotten-Baumann reaction, via nucleophilic substitution reaction of allylthiourea on 4-tertiary-butylbenzoyl chloride. A writhing test was performed to observe analgesic activity in the test compound. Confirmation of the structure of pure 1-allyl-3-(4-tertiary-Butylbenzoyl) Thiourea was obtained through UV, IR, 1H-NMR, and 13C-NMR data. Results: The compound showed better pain inhibition activity compared to diclofenac sodium, with ED5019,018 mg/kg BW. Conclusion: The compound 1-allyl-3-(4-tertiary-butylbenzoyl) thiourea showed better analgesic activity than diclofenac sodium. [ABSTRACT FROM AUTHOR]

Previous studies had shown that ethyl p-methoxycinnamate (EPMS) had various bioactivities, such as analgesic and anti-inflammatory through COX inhibition. Due to its unique structure, this compound was modified into a selective COX-2 inhibitor. In this research, EPMS was isolated from Kaempferia galanga L. and used as a starting material to be reacted with hydrazine hydrate to obtain 3-(4- methoxyfenil)propanehydrazide. This synthesis was carried out using conventional heating and microwave irradiation. The microwave irradiation was chosen because of its potential to reduce reaction time and increase yield. Next, the crude product was purified using column chromatography to produce a pure product, where characterization and structural analyses of the compound were carried out using the TLC test, melting point test, IR, 1H-NMR, and UV spectroscopy. The results showed that the product produced was 3-(4-methoxyphenyl)propanehydrazide with a yield of 0,76% by conventional thermal heating and 7,90% by microwave irradiation. [ABSTRACT FROM AUTHOR]

The estrogen hormone dependent accounts for a major cause in the incidence of women breast cancer. Thus, their receptor, especially the estrogen receptor α (ER-α), is becoming a target in endocrine treatment. These ligand-inducible nuclear functions are regulated by an array of phytochemical and synthetic compounds, such as 17 β-estradiol and tamoxifen (4-hydroxytamoxifen [4OHT]). The Chinaberry (Melia azedarach) leaves are known naturally for relieving internal and external diseases. Previous studies revealed the potency of Melia's ethanolic extract and ethyl acetate fractions as anticancer; furthermore, this study aimed to resolve possible ER-α antagonist's mechanism and safety from M. azedarach leaves ethyl acetate fraction contents. Melia's phytochemical content was analyzed with electrospray ionization liquid chromatography-mass spectrometry, while its ER-α antagonist's potency was investigated by in silico. The computational docking was used to 3ERT (a human ER-α-4OHT binding domain complex) with Autodock Vina and related programs. The results presented Energy binding (ΔG) of Melia's quercetin 3-O-(2'',6''-digalloyl)-β-D-galactopyranoside was similar to 4OHT, and lower than its agonist 17 β-estradiol. Furthermore, the toxicity prediction of these compounds were revealed safer than 4OHT. The Melia's leaves ethyl acetate fraction, therefore, is a potential pharmacological material for further studies. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease. The liposomes were composed of hydrogenated soybean phosphatidylcholine, cholesterol, and distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethyleneglycol]-2000), prepared by thin film method, then evaluated for physicochemical and spectrospic characteristics. The calcein release was further evaluated to determine the effect of drug co-loading on liposomal membrane integrity. The results showed that loading PQ and CQ into liposomes produced changes in the infrared spectra of the diester phosphate and carbonyl ester located in the polar part of the phospholipid, in addition to the alkyl group (CH2) in the nonpolar portion. Moreover, the thermogram revealed the loss of the endothermic peak of liposomes dually loaded with PQ and CQ at 186.6 °C, which is identical to that of the phospholipid. However, no crystallinity changes were detected through powder X-ray diffraction analysis. Moreover, PQ, with either single or dual loading, produced the higher calcein release profiles from the liposomes than that of CQ. The dual loading of PQ and CQ tends to interact with the polar head group of the phosphatidylcholine bilayer membrane resulted in an increase in water permeability of the liposomes. [ABSTRACT FROM AUTHOR]

Introduction: Drugs that inhibit platelet function are antithrombotic agents used in management of arterial thrombosis. Aspirin (acetylsalicylic acid), which blocks platelet is an irreversible inhibitor of cyclooxygenase-1 (COX-1). Some derivatives of coumaric acid decreased the ability of blood clotting and were considered to work through purinergic receptors (P2Y-12). Hydroxyphenyl-carboxylic acids such as coumaric and salicylic acid analogues were great importance in designing new compounds with high antithrombotic activity. This study aimed to inspect the action of thirty designed compounds on platelet aggregation. Methods: Molecular Orbital Environment (MOE) program ver2022.02 was used for docking study and affinity of ligand-protein complex was determined by S-score. The target proteins involved in platelet aggregation were COX-1 (PDB-ID:1CQE), P2Y-12 receptor (PDB-ID:4NTJ), proteinase-activated receptor-1 (PAR-1, PDB-ID:3VW7), and thromboxane receptor (TXA, PDB-ID:6IIU). Top of docked compounds were selected to predict their pharmacokinetic and drug-like properties using SwissADME and OSIRIS online tools. Results: Eleven compounds showed high potential as antiplatelet compared with reference drugs according to their respective target proteins. CA23 showed highest in silico affinities (S< -6.005 kcal/mol) against COX-1, CA18 showed highest affinities (S< -6.144 kcal/mol) on P2Y-12, CA30 showed moderate TXA affinities (S< -7.436 kcal/mol) while all compounds showed lower affinities against PAR-1. The selected compounds possessed good pharmacokinetic profiles with five compounds showed better drug-like properties. Conclusion: Coumaric and salicylic acid derivatives were potential to inhibit platelet through mechanisms on COX-1 and P2Y-12. Coumaric derivatives showed high affinity for P2Y12, while salicylates more active for COX-1 inhibition. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Temu giring, the rhizome of Curcuma heyneana Valeton & Zipj ( C. heyneana ), is native to tropical regions, especially in Indonesia. It is traditionally used as a skin care, for cosmetic and body freshness, in Javanese and Balinese women, and has many other bioactivities such as antioxidant, anticancer and antiinflammatory. Aim of the study The purpose of this study was to determine the antiaging activity of C. heyneana to prove its traditional use. Materials and methods The antioxidant activity was determined using the DPPH free radical method, and anti-aging activity was examined using in vitro assays such as tyrosinase inhibitor and collagenase inhibitor. In vivo tests were performed by observing histomorphologic changes in rat skin exposed to Ultraviolet (UV) rays. The total curcuminoid contents and chromatographic profiles were determined by Thin Layer Chromatography (TLC) – densitometry. Results In all in vitro assays, all of the extracts showed a dose-dependent manner in the final concentration range from 62.5 to 500 µg/mL for DPPH assay and 31.25 to 250 µg/mL for tyrosinase inhibition and collagenase inhibition assay. Curcuminoid (CUR), the active principle of Curcuma genus shows antioxidant, tyrosinase inhibitor and collagenase inhibitor activity greater than all C. heyneana extracts. The in vivo assay results showed that the topical application of the crude extract of C. heyneana produced significant improvement effects on the UV-induced skin structure damage. The total CUR content was correlated with the anti-aging activity of Curcuma heyneana . Conclusions The results show that C. heyneana contains antioxidant compounds and has potent anti-aging activity, indicating that it can be used as an anti-aging drug candidate or as a phyto-cosmeceutical. [ABSTRACT FROM AUTHOR]